Use of certain polyamines as antimicrobial agents

ABSTRACT

USE OF CERTAIN REACTION PRODUCTS OF AMINES AND POLYEPIHALOHYDRINS, SALTS THEREOF AND CORRESPONDING QUATERNARY AMMONIUM DERIVATIVES FOR CONTROLLING MICROORGANISMS.

United States Patent 3,567,420 USE OF CERTAIN POLYAMINES AS ANTIMICROBIAL AGENTS Marvin Legator, Rockville, Md., and Calvin A. Page,

Modesto, Califl, assignors t0 Shell Oil Company, New

York, NY.

N0 Drawing. Continuation of application Ser. No. 513,569, Dec. 13, 1965. This application Apr. 8, 1969, Ser. No. 816,163

Int. Cl. A01n 9/20 US. CI. 7167 9 Claims ABSTRACT OF THE DISCLOSURE Use of certain reaction products of amines and polyepihalohydrins, salts thereof and corresponding quaternary ammonium derivatives for controlling microorganisms.

This application is a continuation of Ser. No. 513,569 filed Dec. 13, 1965, now abandoned.

This invention relates to a method for controlling microorganisms.

In accordance with this invention, it has been found that a particular class of polyamines and certain derivatives thereof are highly toxic to a very broad spectrum of microorganisms.

These new biocidal agents are essentially saturated aliphatic polyamines containing at least one ether moiety. They are characterized by having an essentially saturated aliphatic basic structure in which the linking atoms are carbon together with at least one but never a majority of linking oxy oxygen atoms. The characteristic structural moiety is an alkylene-oxy structure to which is attached at least two aminoalkyl moieties, each containing at least four carbon atoms. Preferably, the polyamine contains at least three such amino moieties. Preferably, there are more than one of the linking oxy oxygen atoms. The corresponding partial and full salts also are suitable, as are the corresponding compounds in which part to all of the aminoalkyl moieties are quaternary ammonium moieties. These new biological agents also suitably may contain middle halogen and/or a minor proportion of nonacidic (i.e., alcoholic) hydroxyl. The basic alkyleneoxy structure may also contain one or more carbonyl moieties, as part of ester structures.

For brevity, these biocides will be referred to hereinafter as polyamines, but this designation is intended to include not only the polyamines per se, but the corresponding quaternary ammonium derivatives and salts mentioned above and described in more detail hereinafter.

*Within this broad class there are certain subclasses that are of particular interest because of their ready availability. Since the character of the new biocidal agents will be more apparent from the manner in which they are preparedby reacting an amine containing at least four carbon atoms 'with a suitable ether precursorthese subclasses of polyamine biocidal agents will be described in terms of the subclasses of suitable ether precursors, which are the following:

(A) Polyepihalohydrins, of which there are seven major genera:

(1) Epihalohydrin dimers and trimers, of the respective formulae:

3,567,420 Patented Mar. 2, 1971 wherein R is the residue of the alcohol, preferably lower alkyl or alkyloxyalkyl (more preferably containing no more than six carbon atoms, and desirably no more than four carbon atoms) and may be substituted by (nm) hydroxyl, and/or one or more middle halogen atoms, and R, R and X have the respective meanings already set out, n is an integer of at least one, m is an integer of at least one, but not exceeding n, and r is an integer which is the number of the moieties within the paratheses occurring within one of the moieties enclosed in brackets, m in number, and r may be zero. Preferably, the molecule contains at least one of the moieties within the parentheses. Where -R is the residue of a monohydric alkyl alcohol, It thus is one, m is one, and r may be zero but preferably is at least one. Where it is the residue of a dihydric alkyl alcohol, n is two, m is one or two and r may be zero but preferably is at least one. Because of the reactivity of the hydroxyls of the alcohol, m ordinarily is two; in one of the two bracketed moieties, r preferably is at least one; it may be zero in the other, or it may be one or greater. r in one bracketed moiety may be the same as r in the other, or it may be different. When n is two and m is one, then R is hydroxyalkyl, since nm=1. Where R is the residue of a trihydric alcohol, n is three, in is one, two or three, r preferably is at least one. Because of the difference in reactivity of the hydroxyls of the alcohol, depending upon their positions on the molecule, the valeus of m and r cannot be predicted. In the case of glycerol, the two hydroxyls bonded to primary carbon atoms ordinarily are of about the same reactivity (as in the dihydric alcohol) and are more reactive than the hydroxyl bonded to the secondary carbon atom. Consequently, when glycerol is used as the initiator, m ordinarily is greater than 2 but less than 3, part of R being hydroxalkyl (nm=1). In either of the two bracketed moieties, in such case, r may be zero, or it may be one or greater. r in one bracketed moiety may be the same as r in the other, or it may be different. In trimethylolethane, and, pentaerythritol, the reactivity of the hydroxyls tends to be about the same, so that m ordinarily is three or four, respectively; r usually is the result of statistical distribution.

The alcohol initiator suitably can contain from one to a plurality of linking oxy oxygen linkages, as in alcohols prepared from polyalkylene oxides, or from glycols wherein one or more but less than all of the hydroxyls have been converted to alkyl ether moieties, as in the Cellosolve ethers and Vcon fluids. Suitable initiators of this general class are disclosed in US. 'Pat. 2,497,315 and 3,190,926. Both the monomeric precursors and the polymeric products described in the former are suitable. Also suitable are the high molecular weight polyoxyalkylene glycols commonly known as Carbowaxes. The alcohol initiator also can suitably contain halogen, as in the polyepihalohydrins and diepoxides of US. Pat. 2,951,854.

Other patents which disclose suitable alcohol-initiated polyepihalohydrins are U.S. Pats. 2,581,464, 2,861,101, 2,891,073, 2,902,398 and 3,058,921, and copending application Ser. No. 381,262.

(3) Water-initiated, which may be represented by the formula:

wherein b and c are integers, b preferably being at least one, the other symbols having the respective meanings already assigned. It is to be noted that water acts as a difunctional initiator.

Polyepihalohydrins of this subclass are disclosed in U.S. Pats. 2,891,073 and 3,058,921, and in British Pat. 898,306.

(4) The corresponding epoxides wherein from one to all of the halohydrin terminal groups,

have been modified to the corresponding epoxide groups,

OHR"CHOHR These may be prepared by conventional methods for epoxidizing halohydrin moieties. Specific examples of suitable members of this subclass are described in U.S. Pats. 2,464,684, 2,891,073, 2,951,854, 3,058,921, 3,078,280 and 3,166,398, and in application Ser. No. 281,262.

Polymerization catalyzed by acidic catalysts, without initiator. The terminal moieties of this class of polyepihalohydrins has not been ascertained with certainty. One is believed to be olefinic in character, with the other believed to be halohydrin in character. These polymers, like those of types 2 through 4 above, are characterized by the repeating moiety:

Examples of members of this subclass are described in U.S. Pats. 2,483,749, 2,599,799, 2,706,182, 2,871,219 and 2,934,505 and British Pat. 477,483.

(6) Polyepihalohydrin epoxides of subclass 4 which have been treated with water and an acid under conditions such as to hydrate the terminal carbon atoms-adding hydroxyl thereto. At least one of the terminal moieties in this case has the formula: CH(OH)CHR(OH). Rodd, Chemistry of Carbon Compounds, volume I p. 650, and Fuson, Advanced Organic Chemistry, p. 230 (1950), illustrate preparation.

(7) Polymerization catalysed by other than an acidic catalyst, no initiator used, as in the polymers of U.S. Pats. 2,706,181, 2,706,189, 2,934,505, 3,026,270, 3,058,- 922, 3,058,923, 3,065,188, 3,078,280, 3,158,580, 2,158,- 581, and 3,190,858, and British Pat. 898,306. Here, also, the terminal moieties are not known with certainty, but the polymers are characterized by the repeating moiety described for subclass 5, above.

(8) Copolymers of epihalohydrins as described above and other alkylene oxides, the oxides having the general formula:

R" 11 v1) wherein each R is hydrogen or alkyl, particularly lower alkyl of from 1 to 5 carbon atoms. These Copolymers have the general formulae set out for the respective subclasses of polyepihalohydrins, with one or more, but less than a major proportion of, the recurring moieties of the polyepihalohydrin being replaced by the moiety This moiety, derived from the alkylene oxide, may replace one or more of the terminal moieties, and/or one or more of the internal moieties of the polyepihalohydrin. Typical members of these copolymers are disclosed in U.S. Pats. 2,706,181, 2,706,182, 2,706,189, 2,871,219, 3,078,280, 3,158,581 and 3,158,591.

The suitable polyepihalohydrins and Copolymers thereof are discussed in some detail in Furukawa and Saegusa, Polymerization of Aldehydes and Oxides, Interscience, 1963.

(B) Polyhaloacetals, having the formula:

L R+ J (1X) wherein R- is lower alkyl, preferably of from 1 to 5 carbon atoms, or is a group represented by R+, which has the meaning already given. Examples of these polymers are set out in U.S. Pats. 2,722,340 and 3,112,280; in British Pats. 758,450 and 797,276; and in Furukawa and Saegusa, (op. cit. supra), pp. 37 (references 54-58 cited therein), Chapter IV, and pp. 368-377 and 430441.

(D) Polyesters, characterized by the recurring moiety of the formula:

wherein R is hydrogen or haloalkyl, with at least one of R being haloalkyl, and 2 has the meaning already assigned. These polyesters are described in U.S. Pat. 3,190,858.

As is disclosed in the references that have been mentioned, ethers of the foregoing kinds, having various molecular weights, are known, varying from bis (2,3- epoxypropyl) ether, molecular weight 130, and epichlorohydrin dimer, molecular weight 197, to polymers of average molecular weight about 300 (m average=1), to about 4500 (m average=50), or even greater, as in the polyepihalohydrins of U.S. 3,158,580, in which the average molecular weight is of the order of 100,000 or greater (n average=about 10001100), for example, up to an average molecular weight of about 1,000,000. As will be demonstrated in the actual examples described hereinafter, a polyamine of a polyepihalohydrin of average molecular weight of the order of 800,000 has been found to be an effective biocidal agent.

It will be appreciated that in the preparation of such polymers, under any given set of preparative conditions, polymers of varying molecular weight will be formed. When molecular weight is indicated in this specification, the average molecular weight of the particular polymer, or fraction of polymeric product, is meant.

Preferred precursors for the preparation of biocides of this invention are the polyepichloroand -bromohydrius and corresponding epoxides initiated by water or a polyol. In the case of the water-initiated poly-epichlorohydrins and epoxides the polyamines of the invention have the amines including the commercial C primary amines formula: marketed commercially under the trade name Prirnene OH OH wherein d and e are integers, and X represents middle 81R, and the commecrial long-chain (lC g primary halogen or amino. amines marketed under the trade name Primene JM-T.

The polyamines prepared from the corresponding gly- The amine suitably can be one of the secondary or tercol-initiated compounds have the formula: tiary amines corresponding to the foregoing primary OH OH wherein R has the meaning already assigned. amines, in which each of the alkyl groups is the same,

Other preferred amines are those prepared from poly or is diflerentas in the cases, for example, of N- (l,4-dihalo-2,3-epoxybutanes) or the corresponding epoxmethyl tert octylamine [by tert octylamine is meant ides of US. Pat. 3,065,188. These polyamines are char- 25 the amine of the formula (CH CCH C(CH NH acterized by the structural moieties. N-methylbutylamine, N,N-dimethylethylamine, and the H EII OH H Internal: O(:3(|J Terminal: H(3?O CH2 (EH2 $H3 (IJHZ X X X X wherein X is middle halogen. These moieties will of like. Alkenylamines and di(alkenyl) amines, such as allcourse be joined together by the residue of the particular ylamine, diallylamine, triallylamine, methallylamine, croinitiator used to prepare them. tylamine, and the like, are suitable; so are mixed alkenyl, A preferred class of polyamines consists of those in alkylamines, such as N-propylallylamine, N-tert-octylall which more than half of the halogen content of the preylamine, N-methylcrotylamine, and the like. Mono-, di,

cursor polyepihalohydrin has been replaced by amino, and tri-cycloalkyl-, mono-, di-, and tri-cycloalkenyland for the polyamines have particularly high microbicidal mixed amines, such as cycloalkyl-alkylamines, cycloalkylactivity. Still more preferably, essentially all of the halodialkylamines and the like, are suitable, typical repregen is replaced by amino, since the resulting polyamines sentative species being cyclohexylamine, N-rnethylcycloappear to exhibit optimum biocidal activity. This is not hexylamine, cyclopentylamine, dicyclopentylamine, cyclo to say that the polyamines containing substantial amounts hexenylamine, N ethylcyclopentylamine and N,N-diof halogen are of less interest, however. It has been found methylcyclohexylamine. The aromatic primary amines, that the halogen content has an eifect on the mammalian and di-aromatic secondary amines are suitable. Suitably, toxicity of the polyamine. In general, mammalian toxithe aromatic group(s) can be substituted by alkyl. T ypicity appears to become less as halogen content increases cal species of these amines include phenylamine, di-

while lower activity toward microorganisms also appears phenylamine, triphenylamine, bis (p methylphenyl) to be associated with higher halogen content, polyamine, 2,4 dimethylphenylamine and the like. Mixed amines contemplated by the invention are so active alkyl arylamines, such as N-methylphenylamine, and N,- toward microorganisms that in some cases over-all use- N-dimethylphenylamine also are suitable. Another suitfulness would dictate use of a polyamine less active able class of amines are those in which one, two or toward microorganisms because of its greater safety, the three hydrocarbon groups is aralkyl, amines such as lesser activity still being sufiicient for the intended purbenzylamine, dibenzylamine, N-methylbenzylamine, N, pose, N-dimethylbenzylamine, phenethylamine, alpha-methyl Essentially any primary hydrocarbon amine or secbenzylamine, N-methyl-alpha-methylbenzylamine, N,N-

ondary di(hydrocarbon) amine of at least four carbon dirnethyl-alpha methylbenzylamine, N phenylbenzylatoms is suitable as the precursor for preparation of amine, N-cyclohexylbenzylamine, and the like.

polyamine biocides of this invention and essentially any Heterocyclic secondary amines also are suitable, protri-hydrocarbon tertiary amine of at least four carbon vided that they contain only one nitrogen, and carbon, atoms or N-hydrocarbon heteroamine is suitable for in the hetero ring. The corresponding N-hydrocarbyl preparation of p0ly(quaternary ammonium) biocides heterocyclic amines also are suitable, the character of of this invention. The hydrocarbon moiety or moieties the N-hydrocarbyl group being that suitable in the other can be aliphatic, including cycloaliphatic, in character, amines already described. Preferably, the N-hydrocarbyl or aromatic in character, or of mixed character. The aligroup is lower alkyldesirably, from 1 to 5 carbon phatic moieties can be of either straight-chain or atoms. Suitable heterocyclic amines thus include, for branched-chain configuration. The aliphatic moieties can example, pyridine, N-methylpyridine, pyrrolidine, piperbe saturated or olefinically unsaturated, but preferably 7 6 idine, N-methylpiperidine, indole, isoquinoline, and the are free from acetylenic unsaturation. Suitable classes like, other suitable amines being mentioned in US. Pat. and species of amines that are suitable thus include the 2,483,749.

following: Alkyl, dialkyl-, and trialkylamines, including The new biocides result from reaction of epoxide linkn-, sec, tertand isobutylamines, the isomeric pentylages of the ether precursor with amines and/or replacearnines, hexylamines, octylamines, decylamines, dodecylment of halogen of the ether precursor by amino moieties. The amino moieties are either secondary or tertiary in character, depending upon whether the amine presursor was primary or secondary in character. In some cases, it will be found that a primary amine may react with more than one halogen, resulting in formation of cyclic tertiarynamino moieties. This will be discussed in more detail hereinafter. Where a tertiary amine is the precursor, the resulting amino moiety is quaternary ammonium in character. Typical polyamines of thisclass are disclosed in US. Pat. 2,483,749 The quaternary ammonium compounds also can be prepared by reacting one of the polyamines in which all or part of the amino moieties are of tertiary character with an alkyl halide, according to conventional procedures.

'Salts of these polyamines also are biocides, in general having properties similar to the corresponding amines. From the standpoint of use as biocides, the salts in some cases may be preferred to the corresponding amines, since the salts may have more useful solubility properties as regards water, organic solvents or other carriers used in the application and administration of biocides. Suitable salts include those of inorganic acids, such as the halogen acids, particularly the hydrohalic acids in particular hydrochloric acid and hydrobromic acid, sulfuric acid, phosphoric acid and boric acid. Both complete: salts and partial salts are suitable. The salts of organic acids also are suitable, examples of suitable acids being the aliphatic monoand polycarboxylic acids, the alkane nnonoand dicarboxylic acids of up to ten carbon atoms being preferred, including those which are substitutedes for example, halogenated acids, hydroxy-substituted acids, and the likealkane and aryl sulfonic acids, phosphonic acids, phosphinic acids, phosphorous acid and its partial esters and the like. Examples of specific acids include acetic acid, succinic acid, lactic acid and gluconic acid. The salts can be prepared in the conventional manner. In the case of the hydrogen halide salts, when polyamines of the invention are prepared il'lzthC manner which has been described, the immediate product of the preparation in many cases is the hydrogen halide saltat least in part.

When an amine is reacted with one of the ether :precursors, it first reacts with epoxide rings, opening the ring, the amino or quaternary ammonium group bonding to the terminal carbon atom, with hydroxyl being bonded to the immediately adjacent carbon atom. If halogen is present, the amine then reacts with the halogen. The amine first reacts with epoxide or halogen bonded to a terminal moiety, then with halogen bonded to an internal moiety. In the biocidal agents of this invention, if terminal epoxide and/or halogen is not present in the ether precursor, then at least two of the halogens on internal moieties must be. replaced by amino.

Where the amine precursor is a primary amine, the resulting polyamine may be at least in part of tertiary cyclic character, the two halogens on the adjacent haloalkylene moieties reacting in part with the amino moiety. Thus, in the case of a polypihalohydrin such as polyepichlorohydrin, the reaction can proceed according to the equation:

In the case of a polyepihalohydrin such as 1,4-dichloro- 2,3-epoxybutane, the reaction can proceed according to the equation:

. 8 Also, it has been found that in the case of the polyepihalohydrins, some cyclization of the amino-alcohol end groups can occur to form dioxane structures of the type:

10 The polyamines are prepared by mixing the ether precursor with an excess of the amine, heating the mixture to a moderately elevated temperature, then holding the mixture at the temperature for a sufiicient period of time to effect the desired degree of reaction of the amine with epoxide and/or replacement of halogen by amino. An often convenient procedure is to supply sufficient of the amine to react with the ether precursor, plus sufiicient excess to act as acceptor for hydrogen halide formed during the reaction, plus sufficient additional excess to'act as solvent. In such operation,, it is desirable to supply at least twice the amount of amine required theoretically by the number of atoms of halogen (and epoxy moieties, if present) with which reaction is desired. Ordinarily, it will not be found of suificient additional: advantage to employ in excess of about six times the amount of amine theoretically required, and in most cases, use of from three to five times the theoretical amount of amine will'be found most desirable. It may in some cases be found desirable to supply an additional solvent. Suitable solvents are those in which the reactants have at least some solubility, and which are inert in the reaction mixture. Suitable solvents include lower alkanols, such as methyl, ethyl, nand isopropyl, butyl and sec-butyl alcohols, lower ketones, such as acetone, methyl ethyl ketone and methyl isobutyl ketone, ethers, such as tetrahydrofuran and dioxane, nitro methane, aromatic or norinally liquid aliphatic hydrocarbons, such as benzene, toluene, xylene, hexane, cyclo- 40 hexane, liquid hydrocarbon fractions, and the like.

It has been found that reaction of amine with epoxide and replacement of halogen by amino in the ether precursors is readily effected at temperatures above about 120 C., with the extent of reaction and replacement being a direct function of time, the rate of replacement being direct function of temperature. Preferably, temperatures of the order of about 140l6-O C. are employed, for at these temperatures the rate of reaction is reasonably rapid, yet is not so rapid as to make difficult 0 termination of the reaction when the desired degree of reaction has been eifected. Temperatures in excess of about 200 C. are preferably avoidedto minimize undesirable side reactions, to insure that decomposition of components of the reaction mixture does not occur, and to reduce the pressure required to maintain the reactants as liquids. Temperatures of the order contemplated are above the boiling points of most amines. Since it is desirable that the reactants be in liquid phase, it consequently is usually necessary to conduct the reaction under such superatmospheric pressure as will maintain theamine, as a liquid. The pressure may be selected to permit refluxing of the amine, if desired, atthough this ordinarily will not be necessary. To establish a criterion for estimating the time required to effect a desired degree of replacement of halogen by amino, it has been found that essentially complete replacement is ordinarily accomplished in about 48 hours, at a reaction temperature of about 150 C.

The polyamine product is worked up conveniently in most cases by first treating the final reaction mixture with dilute aqueous caustic (sodium hydroxide is suitable) to spring the amine from the hydrohalide, then treating the resulting mixture with a suitable solvent, such as ether, to extract and separate the polyamine from the aqueous phase. The ether phase then is dried, and the 9 ether stripped-for example, at 100 C. and 0.1 torr pressure-4o yield the product.

The molecular weight range of the product of course depends primarily upon the molecular weight range of the ether precursor. The desired molecular weight range of the product thus can be accomplished by appropriate choice of precursor. However, it is possible to obtain a product of narrower molecular weight range by appropriate treatment of a product of broader molecular weight range-techniques such as distillation under vacuum, for

example, molecular distillation, chromatography, or treatment with selective solvents, are suitable.

The following examples set forth preparation of specific polyamine biocides of the invention:

EXAMPLE 1 In general, typical polyamines have been prepared by a standard procedure in which the amine, 200-400 percent excess, and the polymer were mixed and reacted at approximately 150 C., under moderate superatmospheric pressure to maintain as a liquid the particular amine used, for about 48 hours. The mixture then was mixed wherein p and q are integers, p+q=7. It had an average molecular weight of 800, containing 32.1% by weight of chlorine. For brevity, it is referred to as polymer Q, referring to Table III.

Typical polyamines are listed in the following table, which indicates the particular amine and ether precursors, and gives any particularly pertinent data on the polyamine. The amine precursors are designated by Roman numerals (reference Table H), the ether precursors by letters (reference Table III) and the polyamines by Arabic numerals (reference Table I), for brevity.

TABLE I Precursors Polyamine Polymer Amine Remarks 1 A V Soluble in acetone. 2 B V De. 3 C IV Soluble in ethanol. 4 C X Soluble in warm ethanol or ether. 5.. D V Soluble in acetone. 6 D IX Do. 7-- E V Do. s E V Hydrochloride salt. Soluble in water. 9-. F XIX Chloride. 1 G IV Soluble in acetone. 11- H IV D0. 12 I III Do.

I V Diaanine. Soluble in acetone.

I V Polyamine. Soluble in acetone. I VI Soluble in acetone. I VIII Soluble in ethanol. I VIII Hydrochloride salt. I X Soluble in acetone. I XXI Do. K V De. L XIX Chloride. Soluble in water. M XXII Do. N I Soluble in acetone. N II Do. N N

V Do. V Higher amine content than 25. Soluble in acetone. V 13.3% chlorine soluble in acetone. V Hydrochloride of 26. Soluble in water. V Lactate of 26. Soluble in water. XVII Soluble in acetone. VII Do. XI Do. XI 18.4% chlorine. Soluble in acetone. XIII Soluble in acetone. XIV Do. XV Do. XVI Do. XVIII Do. XXIII Do. XXIV Do.-

X Soluble in water; XVII Plus methyl iodide. Quaternary ammonium derivative. III Diaun'ne.

Polyalnine. VIII SoluBle in methyl ethyl ketone, acetone.

0. XII Soluble in methyl ethyl ketone, ether. V Soluble in acetone. V Do. V Do. V Do. IV Soluble in methyl ethyl ketone, ether.

1 1 The amines from which these polyamines and quaternary ammonium salts were prepared are listed in the following table.

yeasts, molds, algae and protozoans. They also appear to have some viricidal effect, as well. They have been found to be effective with respect to species of pathogenic TABLE II Amine No. Identity Amine No. Identity 1 n-Butylamine. Primene JM If (Tort-Ci -primary amines) II tert-Butylamine. Oyclohexylamlne.

1I1 n-Heptylamine. beta-Phenethylamine.

IV. n-Oetylamine. N-methyl-butylamine.

V tert-Octylamine. N-methyl-tert-octylamine. VI 1 m XVIII N-methyl-N-oetadccylamino. V1I tert-Nonylamme XIX Pyridine.

VIII- n-Decylamine. XX. Pyrrohdme.

IX n-Undecylamine. L N, N-d1methyl-dodecylamine. X n-Dodecylamine. XXII. N, N -dimethyl-tert-octylamine. XL... Primene 81-R tert-Cn primary amines.

XII n-Tridecylamine.

The ether precursors from which these polyamines were prepared are listed in the following table.

TABLE III PolymerIdentity:

A=Epichlorohydrin linear dimer-1-(2-chloro-1- (chloromethyl) -ethoxy) -2,3 -epoxypropane;

B:1,3-bis(2,3-epoxypropoxy)-2-hydroxypropane;

C=Bis(2,3-epoxypropyl)ether;

D=Water-initiated polyepichlorohydrin diepoxlde,

average molecular weight: 300;

E=Water-initiated polyepichlorohydrin, average mo lecular weight: 350; then distilled to give a higher molecular weight fraction;

F=Water-initiated polyepichlorohydrin, average molecular weight: 350;

G=Water-initiated polymer of 1,4-dichloro-2,3- epoxybutane, average molecular weight: 350; H=Water-initiated polymer of 1,4-dichloro-2,3- epoxybutane, average molecular weight: 400; I=Water initiated polyepichlorohydrin diepoxide,

average molecular weight: 550;

J=Water-initiated polyepichlorohydrin, average molecular weight: 550;

K=Water-initiated polyepichlorohydrin, glycol-terminated, average molecular Weight: 550;

L=Water-initiated polyepichlorohydrin, average molecular weight: 600; then extracted with tolueneinsoluble fraction;

M=Water-initiated polyepichlorohydrin, average molecular weight: 650;

N=Water-initiated polyepichlorohydrin diepoxide, average molecular weight: 800 (this is the ether precursor described in more detail in Example I);

O=Water-initiated polyepichlorohydrin diepoxide,

average molecular weight: 1000;

P=Water-initiated polyepichlorohydrin, glycol-terminated, average molecular weight: 1000;

Q=Glycerol-initiated polyepichlorohydrin, average molecular weight: 1100;

R=Glycerol-initiated polyepichlorohydrin, average molecular weight: 2000;

S Water-initiated polyepichlorohydrin, average molecular weight: 2400;

T=Polyepichlorohydrin, average molecular weight:

The polyamines contemplated by this invention have been found to be very toxic to a nexceptionally broad spectrum of microorganisms, including Gram Positive bacteria, Gram Negative bacteria, Acid Fast bacteria,

microorganisms that have become resistant to control by biocides used heretofore. These polyamines have been found to be essentially nontoxic, dermally and orally, at the biocidally elfective dosage levels. They have been found to retain their activity in the presence of serum and other body fluids, and on surfaces, even though the surface is contaminated by dirt, spilled food, and the like. However, the polyamines have been found to be somewhat phytotoxic at biocidally effective dosages, so that their utility may well be restricted to applications not involving living plants.

Judging from the evidence available regarding their physical, chemical and physiological properties, these polyamines are useful as veterinary pharmaceuticals, as well as for control of microorganisms in situations not involving treatment of animals. Further, since these polyamines appear to be essentially nontoxic with respect to warm-blooded animals at dosages effective against microorganisms, they can be used to preserve foods to be consumed by animals.

To demonstrate the effectiveness of these polyamines as biocides, the following examples are presented.

The general biocidal character of these polyamines their spectra and levels of activity-was ascertained by invitro screening tests employing a variety of different kinds of microorganisms, and a standard concentration of test material amounting to 32 parts per million by weight of the broth medium used. In these tests all of the 52 typical polyamines mentioned in Table I were biostatic or biocidal with respect to one or more of the microorganisms used.

EXAMPLE II Described in more detail, the screening procedure was as follows: a one percent by weight solution of the test compound in a bland solvent (acetone, isopropyl alcohol or the like) was prepared. The solution was aseptically added to a sterile broth that would support the growth of the test microorganism, to provide a concentration of 32 parts by weight of test compound per million parts by weight of broth. A general growth medium such as Trypticase Soy Broth was used. The broth containing the test compound then was dispensed in 5 cubic centimeter amounts into sterile disposable tubes and the tubes were inoculated with an actively growing test organism and incubated at a suitable temperature. After a suitable incubation period, usually 24 hours for bacteria and 72 hours for fungi, the absence or presence of growth of the microorganism was determined. The criterion used for growth: presence or absence of turbidity, sediment, or surface growth, or mycelial development, as determined by visual inspection by an experienced observer.

13 Following is a summary of the results of the testing of typical species of the polyamines described in Table I with respect to some, typical, microorganisms that were employed.

. 14 Algae:

A green alga of the Clorella type. A standard alga growth medium was used. It was found that No. 26 was algastatic at 1-3 p.p.m.; algacidal at p.p.m.

TABLE IV.TEST ORGANISM Species, Type, Gram positive bacteria All gave control. 2

Staphylococcus cureus, Smith strain 1 All gave control.

Staphylococcus aureus, FDA 209 Staphylococcus aureus, Page Diplococcus pneumoniae Streptococcus faecalis All gave control. Bacillus substilis. Do. Listeria monocytogenes 1 Do.

Gram negative bacteria Erwima carotooora l Escherichia coll, Strain B.-. Escherichia coli, ATCC 9637 Salmonella lyphimuriu'm gave control. Salmonella schottmuellerz' 1 50 gave control. Salmonella pullorum 1 Klebsiella pneumoniae L 50 gave control. Proteus vulgar-is 1 Pseudomonas aeruginosa Shiqella jlezneri 1 Acid fast bacteria Mycohacterium aoium Mycobacterzum smegm All gave control.

Penicillium citrinium Trlchophyton mentagrophytes 1 Results, 32 p.p.m. concentration of test compound Do. Nos. 10, 29, and 52 not tested. All others gave control.

Nos. 3, 5, 16, 30, 35, 36 and 52 not tested. All others gave control.

All save Nos. 13, 45, and 52 gave control.

No. 13 not tested. All others save Nos. 6, 15, 45, 50 and 52 gave control.

N o. 13 not tested. All others save Nos. 6, 15, 23, 25, 27, 29, 30, 45, 50, and 52 Nos. 13, 30 and 52were not tested. All others save Nos. 6, 15, 16, 23, 25, 27, and

No. 13 Was not tested. All others save Nos. 23, 27, 45 and 52 gave control. Nos. 13, 23, 25 and 52Were not tested. All others save Nos. 6, 15, 16, 27, 30, 45 and Nos. 23 and 25 were not tested. Nos. 8, 36, and 51 gave control. Nos. 13, 23, 25 and 52 were not tested. No. 13 not tested. All others save Nos. 45 and 52 gave control.

Nos. 3, 8, and 36 gave control.

25, 26, 27, 30, 49, and 52 gave control.

3 6, 8,10,11,16, 25,26, 27, 29, 30, 45, 49 and 50 Nos. 20 and 23 not tested. Nos. 3, 6, 7, 8, 10, 15, 16, 26, 29, 30, 36, 44, 49 and 52 gave 00H Nos. 3, 12, 16, 23, 25, 35, 36 and, 52 not tested. Nos. 27, 29, 30,45 and 51 gave control. Nos. 23 and 25 not tested. Nos. 3, 7, s, 15, 1c, 26, 2e, 30, 4.4 4 Nos. 3, 13, 16, 23, 25, 35, 26 and 52 not tested. Nos. 7, 8, 10, 20, 26, 27, 28, 29, 30, 44,

, 9 and 52 gave control.

48, 49, 50 and 51 gave control.

1 Known to be pathogenic.

2 By control is meant that the test compound was biostatic or biooidal, i.e., no growth of the test organism occurred, under the test conditions.

The character of the biocidal activity of these polyamines is further illustrated by the results of the tests set out in the following examples, wherein Polyamine No. 26, typical of the polyamines, was further tested.

EXAMPLE III In addition to the microorganisms listed in Example II, Polyamine No. 26 was tested and found to control the microorganisms listed in the following table, employing the procedure described in Example II, at a concentration of 32 p.p.m.

Table V Gram positive bacteria:

18 strains or species of Staphylococcus aureus. Several of these strains or species were resistant to the usual antibiotics used to control S. aureus.

9 strains or species of Streptococcus, alpha-hemolytic.

3 strains or species of Streptococcus, beta-hemolytic.

3 strains or species of Diplococcus pneumoniae.

15 strains or species of Escherichia coli.

Gram negative bacteria:

5 strains of Klebsiella pneumoniae.

In each of the above cases, the strain or species was a clinical isolate from a hospital.

Fun gi-molds Aspergillus tamarii Chaetomium globosum Cladosp'o rium resimze Fusarium moniliforme Normodendrium sp. Sclerotz'um rolfsii T richoderma sp. T richophyton tonsurans other species of microorganisms that have been controlled by one or more of the polyamines include:

No. 26 was tested against protozoans by a microscopic observation test. The protozoans used were mixed, nondifferentiated ciliates, flagellates and paramecial types. They were treated with a solution of the polyamine and observed. Control was determined by lack of motion, lack of cytoplasmic streaming and/or other activity. At a dosage of 1 0 p.p.m., No. 26 controlled the protozoans in from 1 to 4 minutes. (No. 28, the hydrochloride salt of No. 26, was even more active, controlling the protozoans in 1 minute or less.)

EXAMPLE V No. 26 was found to be efiective against spores, as well as the vegetative phase of microorganisms. The A.O.A.C. Sporicidal Test Method was used. The test organism was Bacillus subtilis, 7-day culture. It was found that at a dosage of 50 p.p.m., N0. 26 controlled the spores in 9 minutes contact time, as compared to a contact time of 10 minutes for the standard sporicide, 2.5% hydrochloric acid. Further, it was found that the effectiveness of No. 26

'15 was not affected by conducting the test in 20% horse serum. 2

EXAMPLE VI Table VI Organism: 7 3 Inactivation time 7 Staphylococcus aureus,

FDA 209 1 minute.

Streptococcus pyogenes 45 seconds.

Bacillus subtilis, vegetative 7 cells Less than seconds.

7 Bacillus subtilis, spores 9 minutes.

Escherichia coli 7 minutes. Salmonella choleraesuis 9 minutes.

Candida albicans 3.5 minutes.

EXAMPLE VII Tests were conducted to ascertain the influence, if any, of various body materials upon the effect of No. 26 to typical microorganisms. The body materials used were: serum (1), red blood cells (11) and milk (III) each at; a concentration of 5% of the growth medium used and urine (IV) at a concentration of 10% of the medium. "An initial dosage of 32 p.p.m. of No. 26 was used. 7 '7 7 With Staphylococcus aureus, 'FDA 209, none of I, II and IV had any effect, but IIITequired a dosage of 64 p.p.rr r to give control. With Escherichia coli, Strain B, none' of I, II and III had any effect. With Candida albicans and Aspergillus niger, II had' no effect, but I and III required a dosage of 64 p.p.m. to give control. IV was not'included'in the tests against these latter two microorganisms. With Klebsiella pneumoniae, IV had no effect, I, II and; III not being included in the tests Use dilution studies with No. 26 were conducted according to the A.O.A.C. test method. A standard stainless steel cylinder'; coated with asparginine to improve adherence by test organisms, was immersed in a culture for a specified time, then dried for a specified time, then placed in the solution of No. 26 for a specified time, then placed in a sterile tube, and incubated for a specified time, then was examined for growth of the test organism. The test. organism used was Staphylococcus aureus, FDA 209, The results are reported as the concentration of No. 26 in the solution required to control the test organism. In Test A, the growth medium contained no added material. In the other tests, the growth medium contained 10% of an added material, indicated in the following table, which reports the results of the test.

TABLE VII Concentration No. 26 required for control, parts/parts of solvent Added material EXAMPLE IX '16 face involved, and the concentration of No. 26 required to control the organism in each case.

Table VIII Concentration No. 26 required for control Surface: parts/parts of solvent Standard stainless steel 1/25,000 Unpainted wood 1/2500 Painted wood 'l/25,000 Untreated cotton l/5000 Untreated leather I "1/l0,000 Masonite 1/5000 7 Asphalt tile r 1/2500 Rubber tile l/IOOO Porcelain tile 1/2500i EXAMPLE X No. 26* and its salt, No. 28, were tested in various inaterials (10% concentration) by an agar-cup test. A measured amount, of test material was placed in an agar cup, in which the organism, S. aureus FDA 209, had been inoculated, and the zone of inhibition of organism growth was measured. The test materials and results of the tests are set out in the following table. No." 26 was used where oil water solubility was desired.

TAB LE IX Zone of inhibition, W millimeters EXAMPLE XI No. 26 also was screened in vivo tests, with the following results:

(1) Acute oral toxicity, LD milligrams No. 26/lcilogram of animal body weight:

Animal in Mice V 2160 Rats t 1710 Calves and piglets, over 400.

(3) Control of Diplococcus pneumoniue: 30-70% effective against intraperitoneal infections. a I (4) Control of Candida albicans infections in inice: 35- 51% effective against kidneyinfections, drug orally administered. a

EXAMPLE XII No. 26 was shown to control the Newcastle Disease Virus. In this test, the viruswas diluted to 10 in sterile broth, and this dilution was then mixed with a solution of the polyamine and the mixture allowed to stand. At varying intervals of time the mixture was injected into the allantoic cavity of a l0-day chick embryo. This dilution of virus particles, without a drug, ordinarily will cause death of the embryo within 48-72 hours. The polyamine alone, at the concentration used, 'has no effect on the embryo. It was found that at a dosage of 50 p.p.m. No. 26 inactivated the virus following aS-minute contact time.

The results of the tests that have been reported demonstrate the exceptionally broad aaivity of polyamines contemplated in the invention, together with the low mammalian toxicity and other biological, and chemical and physical, properties that establish such polyamines as promising biocides for a wide variety of applications. A few of the applications these polyamines appear to be suitable for include use in proprietary medicines, as in antiseptic ointments, lotions, creams, sprays, tinctures and powders, in germicidal soaps and shampoos; in body deodorants, in cosmetics, hair oils, tonics and dressings, in shaving soaps; as sanitizers, disinfectants and sterilants for use in and around homes, barns, animal pens and shelters, and in hospitals and other public buildings and facilities; in waxes and polishes; as slimicides in industrial process water, such as cOOling water and paper mill waters-to prevent slimesand in controlling undesirable microorganisms in municipal drinking water and recreational Water; in paints and other coatings, sealants, caulking compositions and the like, to prevent deterioration on the shelf and after applied; for preservation of textiles, both during storage and useas in protection of clothing and other cloth articles against attack by mildew, molds and riots when used in tropical or other humid service; to prevent deterioration of plastics; to prevent deterioration of materials used in manufacture and/or preservation of electronic components-potting and insulating compositions and the like; to prevent deterioration of adhesives; to prevent attack of sulfate-reducing bacteria and microorganisms which attack metals, or which cause corrosion of metals; to prevent plugging of underground oil-bearing strata due to the action of microorganisms during secondary recovery; to prevent attack by microorganisms on petroleum hydrocarbon fuels and lubricants; for preventing attack by microorganisms on various non-living useful objects, such as pilings and other structural members of wharves, docks, bridges and the like, books and other documents, leather goods, and the like; as preservatives for animal foods. These in vitro tests show that the subject polyamines control a wide variety of bacteria and other kinds of microorganisms that cause disease in man and/or other animals, so that the polyamines appear to be of interest for protection of animals against a variety of different diseases, the polyamines being used either prophylactically or therapeutically. Because of their very low dermal toxicity to warmblooded animals, the polyamines are of particular interest for controlling skin diseases, and as antiseptics.

The polyamines are applied for each of these purposes by conventional, known means for applying chemicals for those purposes. The polyamines in general are solids or moderately to quite viscous liquids at ordinary room temperatures. Some are soluble to varying degrees in organic liquids, while some are soluble to varying degrees in water. Hydrohalide salts tend to be more water-soluble, as do salts of lower alkanoic acids. The polyamines can be applied neat, or they can be formulated in suitable liquid, solid or aerosol formulations, depending upon the intended usecriteria for selection of suitable carriers for a given use being well known in the appropriate art.

For application for control of microorganisms attacking nonliving material, the polyamine (or mixture of polyamines) may be used alone or in combination with other biocidal agents, such as bactericidal, fungicidal, viricidal, insecticidal and/or acaricidal agents. Wetting agents and, if necessary or desirable, stickers can be included. If the polyamine is to be employed in the form of an emulsion or suspension, for example in water, a cosolvent may be added, or there may be added an emulsifier, emulsion stabilizer or like additive to promote formation and maintain the emulsion or suspension. The formulation may be applied by spraying, dipping, drenching, or other suitable technique. The polyamines also can be formulated as dusts, utilizing as the carrier or vehicle such materials as tricalcium phosphate, precipitated chalk, bentonite, kaolin, kieselguhr, etc. The polyamines also may be applied in the form of aerosols, the polyamine being dissolved or dispersed in a solvent boiling below room temperature at atmospheric pressure. The polyamine can be applied as a solution in a suitable solvent, which may consist of two or more ingredients. In some cases a dosage of as little as 01 part per million of the polyamine in the formulation, thoroughly and uniformly applied to the object to be protected, may be sufficient to control the microorganism in question; however, in most cases, the polyamine dosage probably will be of the order of one part per million or greater. Usually a dosage of 100 parts per million will be sufiicient for control of the microorganism. This is not to say, however, that dosages above that level for example, dosages of the order of 500-1000 parts per million, may not be desirable in some cases simply to insure control. Concentrate formulations may contain much more of the polyamineup to -95 percent, for example. Of course, in some cases, the polyamine itself may be conveniently and effectively used. US. Pat. 3,141,818 describes conventional practice.

The polyamines can be added to foodstuffs or containers to provide protection against attack by bacteria, yeasts, fungal molds and slime molds. As indicated by the experimental evidence, control of such microorganisms can be attained by including in the food a very small concentration of the polyamineconcentrations of the order of one or two parts per million in some cases being sufficient, with concentrations of from about 5 to about 500 parts per million by Weight of the food being generally suitable, and concentrations of from about 20 to about 200 parts per million generally being optimum. In the majority of cases, a concentration greater than 1% by weight will not be required. A water solution of a water soluble polyamine or salt of a polyamine can be used, or it can be dispersed in water, or a solution of the polyamine in a suitable bland, palatable organic solvent can be used. If desired, edible emulsifying agents can be used. The polyamine can be incorporated in such carriers as vegetable oils, fats and the like, in gelatin, pectins or the like. If desired, the polyamine can be dissolved or dispersed in water, the solution or dispersion frozen, and the frozen material used in packing the food product. Solid compositions containing the polyamine can be obtained by incorporating it with a finely divided edible solid, such as milk solids, flours and the like. Any suitable and convenient technique can be used to attain and insure the necessary intimate association of the polyamine and the food product to be protected. Thus, the polyamine can be incorporated into the food product, as by mixing the polyamine with the food product. For example, hamburger, sausage and other ground meat products can be readily protected in this way. Where the food product is formed, and is essentially sterile, attack by microorganisms can be inhibited by coating the surface of the food product. To effect this coating, the food product can be dipped in a liquid or semiliquid composition of the polyamine, or washed or sprayed or painted with such a liquid or semiliquid composition, or it can be dusted with a solid composition containing the polyamine. The polyamine can be incorporated in or on materials used for wrapping the food productspaper, parchment, cloth or other porous materials used for wrapping or gelatinous materials used for coating the food products can be impregnated with the polyamine, and foil or plastic film and other non-porous wrapping materials can be coated with a polyamine. Conventional practice is illustrated in US. Pat. 3,044,884.

The polyamines can be used to control noxious microorganismsfor example, slime-forming microorganisms in water, again by conventional techniques, which are illustrated in US. Pat. 3,006,807. The polyamines can be used to control sulfur bacteria, iron bacteria and bacteria which cause corrosion of metals by conventional techniques, which are illustrated in US. Pats 3,141,818, 3,089,847, and US. 2,987,475. These patents also illustrate conventional techniques for applying chemicals to water used in secondary oil recovery from oil wells, to

prevent plugging of oil-bearing strata as does US. Pat. in excess of the amount theoretically required to replace 3,049,492; the polyamines also can be used for such the halogen and epoxy moieties, if present in the polyepipurpose, by such techniques. halohydrin, said heating being continued to form a prod- In general, it is necessary only to introduce one or more uct having the formula of the polyamines into the water to be treated, to provide or acid salts thereof where in the amino moiety is selected the biocidally effective dosage. In some cases, this dosage from the group consisting of a secondary hydrocarbon Will be as little as 0.5 part per million parts by weight of substituted amine and a tertiary dihydrocarbon substituted the water to be treated, while in other cases a dosage of amine each hydrocarbon having from 1 to 22 carbon as much as 250 parts per million may be required. Genatoms with the proviso that each amino moiety must conerally, the elfective dosage will be found to lie within the tain at least 4 carbon atoms and be free of acetylenic un range of from about 5 to about 100 parts per million. saturation; X is selected from the group consisting of The polyamines can be used in the treatment of Warmamino, chloro and bromo and d and e are integers such blooded animals, such as livestock and other domestic that the average molecular weight of the polyhalohydrin animals. The polyamines can "be administered by convenstarting material is from about 130 to about 1,000,000. tional techniques, the polyamine being used neat or for- 2. The method according to claim 1 wherein X and mulated by conventional techniques in suitable formulaamino are both NH(tert-octy1). tions conventionally employed for treating the particular 3. The method accordin to claim 2 wherein the polyanimal for the particular disease. Compositions suitable epihalohydrin is polyepichlorohydrin diepoxide having an for treatment of animals include in addition to the polyaverage molecular weight of about 800. amine pharmaceutical or veterinary carriers which may 4. The method according to claim 3 wherein the microeither be solid or liquid materials. Preparations can be organisms are controlled by administering said reaction liquids or solids or any combination of these forms, such product or acid salt thereof orally or dermally to a warmas syrups, elixirs, emulsions, ointments, lotions, creams, blooded animal. sprays, tinctures, powders, capsules or tablets, or they 5. A method of controlling microorganisms selected can be incorporated in germicidal soaps, or other prepfrom the group consisting of bacteria, fungi, algae, proarati n tozoans and spores comprising contacting said microor- The polyamine suitably, for example, can be mixed ganisms with a biocidally efiective quantity of the product into the feed of animals or given in their drinking water. formed by reacting: As little as 0 .1 milllgram per kilogram of body weight (a) a member Selected from the group consisting of may be sufficlent or as much as 100 mllllgrams per klloa primary hydrocarbon substituted amine and a body Weight may p y AS feed ()Tf/Vater 4O ondary dihydrocarbon substituted amine; with addltivies a dosage of as low as 0.5 part per million or a polyepihalohydrin selected from the group com as h1 gh as 500 Parts P mlllllon of the Compound may be sisting of a polyol initiated polyepichlorohydrin, Ieqlllredpolyol initiated polyepibromohydrin, polyol initiated Composltrons of compounds of thls inventlon andsurtpolyepichlorohydrin epoxide and polyol initiated able mert carriers, VBhICIGS, or d1luents may contain as polyepibromohydrin epoxide, g gfi OOOOIIZJ of the active mgredlent or as much as said reaction being effected by heating at a temperature 0 of the active compound. of from about C t b 20 o We claim as our invention: o a out 0 a Q 1 A method of controllin microorganisms selected the POlYeplhalohYdnn and the amme the amme belng iron-1 the group consisting of l jacteria fungi algae ro present in excess of the amount theoretically required to t n d S 0 t i d replace the halogen and epoxy moieties if present 1n the Zoa s an Pores compnsme con ac mg Sal mlcro polyepihalohydrin, sa1d heating being continued to form a product having the formula 1 (EH2 6112 X 1 r 8 organisms with a biocidally effective quantity of the or acid salts thereof wherein the amino moiety is selected product formed by reacting: from the group consisting of a secondary hydrocarbon substituted amine and a tertiary dihydrocarbon substituted a a member selected from the rou consistin of g P g amine each hydrocarbon havin from 1 to 22 carbon a primary hydrocarbon substituted amine and a secondary dihydrocarbon substituted amine, with atoms with thfi Proviso that each amino moiety must (b) a polyepihalohydrin selected from the group o contain at least 4 carbon atoms and be free of acetylenic sisting of a water initiated polyepichlorohydrin, waunsaturation, R is the residue of a polyol containing no l initiated polyepibromohydrin, Watfif initiated more than 6 carbon atoms, X is selected from the group polyepibr0m yd Water initiated polyepichlorohy' consisting of amino, chloro and bromo and d and e are drin egoXid a Water initiated polyepi'bromohydrin integers such that the average molecular weight of the BPOXI polyhalohydrin starting material is from about 130 to said reaction being effected by heating at a temperature about of from about 120 C. to about 200 C. a mixture of the A composition adapted to control microorganisms polyepihalohydrin and the amine, the amine being present selected from the group consisting of bacteria, fungi, al-

21 gae, protozoans and spores which comprises 0.0001 to' (b) a'polyepihalohydrin selected from the group con- 95% by weight of a product formed by reacting: sisting of a polyol initiated polyepichlorohydrin, (a) a member selected from the group consisting of a polyol initiated polyepi'bromohydrin, polyol initiated primary hydrocarbon substituted amine and a seconp y p hy in P de and polyol initiated dary dihydrocarbon substituted amine; with 5 polyepibromohydrin epoxide, (b) a polyepihalohydrin selected from the group consaid reaction being effected by heating at a temperature sisting of a water initiated polyepichlorohydrin, 0f f OIn about 120 C. to about 200 C. a IniXtureOf Water initiated polyepibromohydrin, water initiated the pelyeplhalohydrm and the amlne, the amlne bemg polyepichlorohydrin o id w t i iti t d polyepipresent in excess of the amount theoretically required to bromohydrin epoxide, 1O replace the halogen and epoxy moieties, if present in the said reaction bein eifected by heating at a temperature polyepihalohydrin, said heating being continued to form of from about 120 C. to about 200 C., a mixture of a product having the formula OH OH the polyepihalohydrin and the amine, the amine being or acid salts thereof wherein the amino moiety is selected present in excess of the amount theoretically required to from the group consisting of a secondary hydrocarbon replace the halogen and epoxy moieties, if present in the substituted amine and a tertiary dihydrocarbon substituted polyepihalohydrin, said heating being continued to form amine each hydrocarbon having from 1 to 22 carbon a product having the formula 25 atoms with the proviso that each amino moiety must con- Ki? ,K if),

or acid salts thereof wherein the amino moiety is selected tain at least 4 carbon atoms and be free of acetylenic unfrom the group consisting of a secondary hydrocarbon saturation, R is the residue of a polyol containing no substituted amine and a tertiary dihydrocarbon substimore than 6 carbon atoms, X is selected from the group tuted amine each hydrocarbon having from 1 to 22 carconsisting of amino, chloro and bromo and d and e are 'bon atoms with the proviso that each amino moiety must integers such that the average molecular weight of the polyhalohydrin starting material is from about 130 to about 1,000,000 and an inert carrier.

contain at least 4 carbon atoms and be free of acetylenic unsaturation, X is selected from the group consisting of amino, chloro and bromo and d and e are integers such that the average molecular weight of the polyhalo- Ref Cited hydrin starting material is from about 130 to about UNITED STATES PATENTS 1,000,000 and an inert carrier.

7. The composition according to claim 6 wherein X 3 2,560,280 7/ 1951 De Bennevllle 260567.6 d amino are both 1 3,331,788 7/1967 Lorensen et al. 260-2 8. The composition according to claim 7 wherein the 3,372,129 3/ 1968 l lps 260567.6

polyepihalohydrin is polyepichlorohydrin diepoxide having an average molecular Weight of about 800.

9. A composition adapted to control microorganisms selected from the group consisting of bacteria, fungi, algae, protozoans and spores which comprises 0.0001 to US. Cl. X.R.

95% by Weight of a product formed by reacting: 5703 570.9 571 424 78 (a) a member selected from the group consisting of O a primary hydrocarbon substltuted amine and a secondary dihydrocarbon substituted amine; with ALBERT T. MYERS, Primary Examiner 50 V. D. TURNER, Assistant Examiner 

